REVIEW

Hypolipidemic, Antioxidant, and Antiinflammatory Activities

of Microalgae Spirulina
Ruitang Deng1 & Te-Jin Chow2
1 Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI, USA
2 Department of Biotechnology, Fooyin University, Kaohsiung, Taiwan

Keywords
Antioxidant; Antiinflammatory; Hypolipidemic;
Lipids disorder/atherosclerosis; Spirulina.
Correspondence
Dr. Ruitang Deng, Department of Biomedical
and Pharmaceutical Sciences, College of
Pharmacy, University of Rhode Island,
41 Lower College Road, Kingston,
RI 02881, USA.
Tel.: 401-874-4950;
Fax: 401-874-5787;
E-mail: DengR@mail.uri.edu
doi: 10.1111/j.1755-5922.2010.00200.x
SUMMARY
Spirulina is free-floating filamentous microalgae growing in alkaline water bodies. With its
high nutritional value, Spirulina has been consumed as food for centuries in Central Africa.
It is now widely used as nutraceutical food supplement worldwide. Recently, great attention
and extensive studies have been devoted to evaluate its therapeutic benefits on an array of
diseased conditions including hypercholesterolemia, hyperglycerolemia, cardiovascular dis-
eases, inflammatory diseases, cancer, and viral infections. The cardiovascular benefits of
Spirulina are primarily resulted from its hypolipidemic, antioxidant, and antiinflammatory
activities. Data from preclinical studies with various animal models consistently demonstrate
the hypolipidemic activity of Spirulina. Although differences in study design, sample size,
and patient conditions resulting in minor inconsistency in response to Spirulina supplemen-
tation, the findings from human clinical trials are largely consistent with the hypolipidemic
effects of Spirulina observed in the preclinical studies. However, most of the human clinical
trials are suffered with limited sample size and some with poor experimental design. The
antioxidant and/or antiinflammatory activities of Spirulina were demonstrated in a large
number of preclinical studies. However, a limited number of clinical trials have been car-
ried out so far to confirm such activities in human. Currently, our understanding on the
underlying mechanisms for Spirulina’s activities, especially the hypolipidemic effect, is lim-
ited. Spirulina is generally considered safe for human consumption supported by its long
history of use as food source and its favorable safety profile in animal studies. However,
rare cases of side-effects in human have been reported. Quality control in the growth and
process of Spirulina to avoid contamination is mandatory to guarantee the safety of Spirulina
products.

Early studies were mainly focused on the nutritional value

Introduction
Spirulina is referred to free-floating filamentous microalgae
with spiral characteristics of its filaments. It is formally called
Arthrospira, belonging to the class of cyanobacteria with charac-
teristic photosynthetic capability [1,2]. Spirulina was initially clas-
sified in the plant kingdom because of its richness in plant pig-
ments as well as its ability of photosynthesis. It was later placed
in the bacteria kingdom based on new understanding on its ge-
netics, physiology, and biochemical properties [3]. Spirulina nat-
urally grows in high-salt alkaline water reservoirs in subtrop-
ical and tropical areas including America, Mexico, Asian, and
Central Africa [3,4]. Among large number of Spirulina species,
three species of Spirulina, including Spirulina platensis (Arthrospira
platensis), Spirulina maxima (Arthrospira maxima), and Spirulina
fusiformis (Arthrospira fusiformis) are most intensively investigated
as those Spirulina species are edible with high nutritional as well
as potential therapeutic values [3–6].
of Spirulina as a food source. As early as over 400 years ago,
Spirulina was eaten as food by the Mayas, Toltecs, and Kanembu
in Mexico during the Aztec civilization [7]. Spirulina growing
in the Lake Texcoco were harvested, dried and used to make
Spirulina cake as food. It has also been over centuries for the
Chadian to consume Spirulina in Central Africa. Spirulina har-
vested from the Lake Kossorom (Chat) is used to make cake or
broths as meals and also sold on the market [8]. The nutritional
value of Spirulina is well recognized with its unusual high pro-
tein content (60–70% by dry weight) and its richness in vitamins,
minerals, essential fatty acids, and other nutrients [3,4]. Because
of its unusual high nutritional values, the Intergovernmental In-
stitution for the use of Micro-algae Spirulina Against Malnutrition
(IIMSAM) was launched in the middle 1970s to promote Spirulina
as high nutritional food to fight against starvation and malnutri-
tion in the world [9]. In addition, due to its concentrated nutrition,
Spirulina was recommended by both National Aeronautics and Space

Cardiovascular Therapeutics 28 (2010) e33–e45 

c 2010 Blackwell Publishing Ltd e33

Hypolipidemic, Antioxidant, and Antiinflammatory Activities of Microalgae Spirulina
Administration (NASA) and the European Space Agency (ESA) as
one of the primary foods during long-term space missions.
Starting at middle 1980s, great efforts and extensive investi-
gations have been turned to the development of nutraceuticals
or functional food for preventing or managing various diseases.
Spirulina has become one of such nutraceutical food with diverse
beneficial effects on an array of disease conditions. It has been
reported that consumption of Spirulina as diet supplement has
health benefits in preventing or managing hypercholesterolemia,
hyperglycerolemia, certain inflammatory diseases, allergies, can-
cer, environmental toxicant- and drug-induced toxicities, viral in-
fections, cardiovascular diseases, diabetes, and other metabolic dis-
ease among others [5,6,10]. In this review, emphasis is given to
the potential beneficial effects of Spirulina on cardiovascular dis-
eases with highlights on Spirulina’s hypolipidemic, antioxidant,
and antiinflamatory activities in preclinical and clinical studies.
In addition, our current understanding on the mechanisms of ac-
tion and the potential side-effects of Spirulina consumption are
summarized.
Hypolipidemic Effects
Cholesterol is the building block for cell membrane and a pre-
cursor of steroid hormones. It forms several distinct particles with
lipoproteins, mainly high-density lipoproteins (HDL), low-density
lipoproteins (LDL), and very low-density lipoproteins (VLDL). It is
well established that LDL and VLDL cholesterol levels are athero-
genic whereas HDL-cholesterol has protective effects on the devel-
opment of atherosclerosis [11,12]. Increased LDL and VLDL levels
are the major independent risk factor for cardiovascular events
whereas low level of HDL and elevated triglycerides (TG) are also
recognized as residual risk for cardiovascular diseases [13]. Agents
with the ability to decrease LDL/VLDL or total cholesterol levels,
increase HDL cholesterol or lower TG have beneficial effects on
preventing cardiovascular diseases.
Preclinical Studies
The hypolipidemic effect of Spirulina or its extracts have been
demonstrated in various animal models including mouse, rat,
hamster, and rabbit. The cholesterol lowering activity of Spirulina
was first reported in albino rats [14], followed by in mice [15].
In the mouse study, supplementation of 16% Spirulina in a high
fat and cholesterol diet resulted in a significant reduction in to-
tal serum cholesterol, LDL, VLDL cholesterol, and phospholipids
whereas serum HDL cholesterol was concurrently increased. In
addition, high hepatic lipids induced by the high fat and choles-
terol diet were markedly reduced by Spirulina consumption [15].
Since the initial report of hypolipidemic effects of Spirulina, sev-
eral in vivo studies were carried out in rats and mice under various
experimentally induced conditions. In one study [16], hyperlipi-
demia was induced in Wistar rats by a high fructose (68%) diet.
Inclusion of increasing percentages of Spirulina (5%, 10%, and
15%) in the diet significantly improved the hyperlipidemic pro-
files. Correlating with such improvement in lipid profiles, Spirulina
feeding resulted in a significant increase in lipoprotein lipase and
hepatic triglyceride lipase activity. Such increased lipase activity
e34
17555922, 2010, 4, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/j.1755-5922.2010.00200.x by Ministry Of Health, Wiley Online Library on [31/10/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
R. Deng and T.-J. Chow
by Spirulina was suggested as a mechanism for improving the hy-
perlipidemia induced by high fructose diet. In another study with
rats [17], fatty liver was induced by intraperitoneal injection of
carbon tetrachloride (CCl4 ), resulting in an increase in liver total
cholesterol and triacylglycerols. However, such increases were sig-
nificantly reduced by feeding oil extracts of Spirulina or defatted
fraction of Spirulina. In addition, CCl4 -induced increase in total
cholesterol level was completely prevented by feeding a diet con-
taining whole Spirulina. A similar study was performed in CD-1
mice [18]. Fatty liver was induced by a daily dose of simmvastatin
(75 mg/kg body weight) for 5 days with a high cholesterol diet and
20% ethanol in the drinking water. Serum and hepatic triacylglyc-
erols, total lipids and cholesterol were all significantly increased.
However, Spirulina feeding for 2 weeks prior to the onset of fatty
liver induction decreased hepatic total lipids by 40%, triacylglyc-
erols by 50%, and serum triacylglycerols by 45%, accompanied by
a 45% increase in serum HDL cholesterol. The hypolipidemic ac-
tivity of Spirulina was also confirmed in a diabetic mouse model
[19]. Diabetic condition was induced by administration of alloxan
(250 mg/kg body weight), resulting in evident fatty liver accompa-
nied by altered serum and hepatic triacylglycerols and cholesterol
levels. However, mice receiving a diet containing 5% Spirulina 1
week after the administration of alloxan for 4 weeks totally pre-
vented fatty liver production, decreased serum and hepatic triacyl-
glycerols, and fully or partially normalized HDL, LDL, and VLDL
cholesterol levels. The study also showed that female mice were
more resistant to diabetes induction by alloxan whereas more re-
sponsive to Spirulina treatment than male mice.
The hypolipidemic effects of Spirulina observed in mice and rats
were verified in two recent studies with hamsters [20] and rabbits
[21]. A group of hamsters fed an atherogenic diet supplemented
with Spirulina or its ingredient phycocyanin exhibited lower total
cholesterol, LDL, and VLDL cholesterol whereas HDL cholesterol
was not affected. Furthermore, aortic fatty streak area was signif-
icantly reduced in hamsters receiving Spirulina supplement, indi-
cating the antiatherogenic activity of Spirulina [20]. In the study
with rabbits, hypercholesterolemia was induced by a high choles-
terol diet and the effects of feeding Spirulina (0.5 g daily) for 30 and
60 days on the induced hypercholesterolemia was evaluated [21].
At the end of the study, serum total cholesterol was decreased by
49% while HDL cholesterol was increased by 25%. No significant
changes in serum triacylglycerols were observed.
Taken together, the results from studies with various animal
models consistently demonstrate the hypolipidemic activity of
Spirulina, lowering serum total cholesterol, LDL, and VLDL frac-
tions. In addition, other improvements in lipid profile were also
observed in certain studies, including an increase in HDL choles-
terol levels, decrease in atherogenic indices and triacylglycerol
levels.
Clinical Studies
A number of human clinical trials have been performed to eval-
uate the hypolipidemic activity of Spirulina (Table 1). The target
populations include healthy volunteers, patients with ischaemic
heart disease, type 2 diabetes and nephrotic syndrome, and elderly
subjects with or without hypercholesterolemic condition.
Cardiovascular Therapeutics 28 (2010) e33–e45 
c 2010 Blackwell Publishing Ltd

R. Deng and T.-J. Chow
Table 1 Hypolipidemic effects of Spirulina in human clinical studies
Subject
Healthy volunteers (Male)
Patinets with ischaemic
heart disease
Patients with type 2
diabetes mellitus
Patients with type 2
diabetes mellitus
Patients with nephrotic
syndrome
Healthy volunteers
Healthy elderly volunteers
Elderly Women with
hyperchole-sterolemia
Patients with type 2
diabetes mellitus
Cardiovascular Therapeutics 28 (2010) e33–e45 
17555922, 2010, 4, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/j.1755-5922.2010.00200.x by Ministry Of Health, Wiley Online Library on [31/10/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
Hypolipidemic, Antioxidant, and Antiinflammatory Activities of Microalgae Spirulina
Sample Size Dose of Spirulina Duration Effects of Spirulina Reference
30 4.2 g, Daily 4 or 8 weeks Total serum cholesterol and LDL were reduced [22]
significantly. Triglyceride levels decreased slightly
whereas HDL-cholesterol showed no significant
changes. The reduction of serum cholesterol was even
greater in those men with the highest cholesterol levels.
30 2 or 4 g, Daily 3 months Total plasma cholesterol, LDL, VLDL and triglycerides [24]
were significantly reduced by 22.4% (2 g group)/33.5%
(4 g group), 31%/45%, 22%/23%, and 22%/23%,
respectively. HDL was significantly increased by
11.5%/12.8%. In addition, a significant reduction in body
weight was achieved in both treatment groups.
15 2 g, Daily 2 months A significant reduction was detected in triglycerides, [25]
total cholesterol and free fatty acid levels. LDL and VLDL
were also decreased. In addition, blood sugar and
glycated serum protein levels were significantly
decreased.
25 2 g, Daily 2 months Total serum cholesterol and LDL fraction were reduced [26]
whereas HDL was slightly increased. As a result, a
significant decrease in atherogenic indices and the
ratios of total cholesterol/HDL and LDL/HDL was
observed. Furthermore, triglycerides and fasting and
postprandial blood glucose levels were significantly
reduced. Finally, the level of apolipoprotein B showed a
significant fall with a concurrent significant increase in
the level of apolipoprotein A1.
23 1 g, Daily 2 months Total serum cholesterol, LDL cholesterol and [29]
triglycerides were all significantly decreased by
46 mg/dL, 33 mg/dL, and 45 mg/dL, respectively. The
ratios of LDL/HDL and total cholesterol/HDL were also
decreased significantly.
36 4.5 g, Daily 6 weeks Total plasma cholesterol and triacylglycerols were [23]
significantly reduced by 10% and 28%, respectively. HDL
was significantly increased by 15% whereas LDL
cholesterol was significantly decreased. In addition,
both systolic and diastolic blood pressures were
significantly reduced in both men and women.
12 7.5 g, Daily 24 weeks The plasma concentrations of triglycerides, total [33]
cholesterol and LDL cholesterol were decreased after
4 weeks of the supplementation. No differences in
hypolipidemic effects of Spirulina were observed
between mild hypercholesterolemic (cholesterol at or
above 200 mg/dL and normocholesterolemic subjects.
51 7.5 mg, Daily 8 weeks Serum levels of total cholesterol, LDL cholesterol and [34]
oxidized LDL were significantly reduced. In addition,
apolipoprotein B, IL-6, and IL-6 production by peripheral
blood lymphocyte were also decreased.
37 8 g, Daily 12 weeks Total serum cholesterol, LDL fraction and triglycerides [27]
were reduced with the subjects with higher initial total
cholesterol, LDL-cholesterol and triglycerides showing
higher reduction. In addition, blood pressure and IL-6
levels were also decreased. Finally, a significant
reduction in plasma malondialdehyde level was
observed.
c 2010 Blackwell Publishing Ltd e35

Hypolipidemic, Antioxidant, and Antiinflammatory Activities of Microalgae Spirulina
Table 1 Continued
Subject Sample Size Dose of Spirulina Duration
Patients with type 2 60 1 or 2 g, Daily 2 months
diabetes mellitus
Healthy elderly volunteers 78 8 g, Daily 16 weeks
The first human study was carried out in 1988 with 30 healthy
male volunteers with mild hyperlipidemia or hypertention [22].
The 30 subjects were divided into two groups; one group received
4.2 g of Spirulina daily for 8 weeks whereas the other group was
given Spirulina for 4 weeks, followed by on regular food for an-
other 4 weeks. Intake of Spirulina for 4 or 8 weeks significantly de-
creased total serum cholesterol and the decrease was more marked
in mild hypercholesterolemic than in normocholesterolemic sub-
jects. Discontinuation of Spirulina supplement for 4 weeks resulted
in returning of the cholesterol level to the baseline (prior to Spir-
ulina supplementation) and HDL levels were slightly increased
but not statistically significant. There were no changes in serum
triglycerides and body weight. In addition, no subjects reported ad-
verse effects during the study. In a recent before-and-after clinical
trial with 36 healthy volunteers (16 male and 20 female) between
ages 18 to 65 [23], ingestion of Spirulina at a dose of 4.5 g daily
for 6 weeks decreased total plasma cholesterol and triacylglycerols
by 10% and 28%, respectively. Lipoprotein analysis showed that
HDL cholesterol was increased by 15% whereas LDL cholesterol
was significantly decreased. In addition, both systolic and dias-
tolic blood pressures were significantly reduced in both men and
women.
The hypolipidemic effect of Spirulina was also demonstrated in
ischaemic heart disease patients with hypercholesterolemic con-
dition (serum total cholesterol levels above 250 mg/dL) [24], a
total of 30 patients were divided into three groups. Two treatment
groups received 2 or 4 g of Spirulina daily for 3 months whereas
control group was not supplemented with Spirulina. At the end
of the supplementation, plasma total cholesterol was significantly
decreased by 22.4% and 33.5% in groups receiving 2 and 4 g Spir-
ulina, respectively, whereas no significant change was detected in
the control group. Lipoprotein fraction analysis showed that LDL
and VLDL cholesterol levels were significantly reduced by 31%
and 45%, and 22% and 23% in the two treatment groups, re-
spectively. On the other hand, HDL was significantly increased by
11.5% and 12.8%. Furthermore, the concentration of triglycerides
was significantly reduced by 22% and 23%. Finally, a significant
loss in body weight was observed in both treated groups whereas
no change was detected in the control group. Thus, it was con-
e36
17555922, 2010, 4, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/j.1755-5922.2010.00200.x by Ministry Of Health, Wiley Online Library on [31/10/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
R. Deng and T.-J. Chow
Effects of Spirulina Reference
A significant decrease was observed in serum total [28]
cholesterol, triglycerides, LDL, and VLDL cholesterol in
Spirulina treatment groups. In addition, both fasting and
postprandial blood glucose levels were also significantly
decreased accompanied with decreased mean
carbohydrate and protein intake.
Total plasma cholesterol and LDL fraction were [35]
significantly reduced in female subjects whereas a
significant lowering effect on plasma total cholesterol
by repeated test for treatment was observed in male
subjects. However, no significant effect was detected in
LDL fraction in male subjects. The levels of HDL fraction
and triglycerides did not change after the intervention
in both men and women
cluded that supplementation of Spirulina at a daily dose of 2 or 4 g
for 3 months significantly improved the lipid profile of the patients
with ischaemic heart disease.
Noninsulin-dependent diabetes mellitus (NIDDM) or type 2 dia-
betes mellitus is a recognized independent risk factor for cardiovas-
cular diseases, such as coronary artery disease. The distinction be-
tween type 2 diabetes mellitus and cardiovascular disease has been
blurred and prevention of cardiovascular diseases is becoming an
integrated part of diabetes management. Patients with type 2 di-
abetes are frequently affected by atherosclerotic vascular disease.
The abnormalities of both quantity and quality of lipoproteins in
type 2 diabetes patients contribute to an increase in atherosclerotic
vascular disease. So far, four human clinical studies have been per-
formed to investigate the hypolipidemic and hyperglycerolemic ef-
fects of Spirulina in type 2 diabetic patients [25–28]. The two early
studies were carried out by Dr. Iyer’s group in India [25,26]. In a
before-and-after study with 15 type 2 diabetes patients [25], sup-
plementation of Spirulina at a dose of 2 g daily for 2 months re-
sulted in a significant decrease in total serum cholesterol, triglyc-
erides, and free fatty acid levels. Analysis of lipoprotein fractions
revealed that LDL and VLDL cholesterol levels were appreciably
reduced. Blood sugar and glycated serum protein levels were also
significantly decreased. In a second randomized and controlled
study [26], 25 patients with type 2 diabetes mellitus were ran-
domly assigned to a study or control group. Subjects in the study
group received Spirulina at a dose of 2 g/day for 2 months. At the
end of the study, total serum cholesterol and LDL fraction were re-
duced whereas HDL was slightly increased in the study group. As
a result, a significant decrease in atherogenic indices and the ra-
tios of total cholesterol/HDL and LDL/HDL was achieved. Triglyc-
erides and fasting and postprandial blood glucose levels were sig-
nificantly reduced. Finally, the level of apolipoprotein B showed a
significant fall with a concurrent significant increase in the level of
apolipoprotein A1. Thus, the hypolipidemic and hypoglycerolemic
effects of Spirulina were consistently detected in both clinical stud-
ies with type 2 diabetic patients.
The findings from the early studies were confirmed in the two
recent human clinical trials with type 2 diabetic patients [27,28].
Both trials were randomized, controlled studies with a relatively
Cardiovascular Therapeutics 28 (2010) e33–e45 
c 2010 Blackwell Publishing Ltd

R. Deng and T.-J. Chow
large sample size. One study enrolled 37 patients being randomly
divided into a treatment or control group [27]. Intake of Spirulina
at a dose of 8 g daily for 12 weeks significantly reduced total
serum cholesterol, LDL fraction, and triglyceride levels. Subjects
with higher initial total cholesterol, LDL-cholesterol, and triglyc-
eride levels showed higher reduction. In addition, blood pressures
were also decreased. The second trial included 60 male patients ag-
ing from 40 to 60 years [28]. The subjects were randomly assigned
into two treatment groups or a control group. The two treatment
groups received 1 or 2 g Spirulina daily for 2 months. A significant
decrease was observed in serum total cholesterol, triglycerides,
LDL and VLDL cholesterol in the two treatment groups. Both fast-
ing and postprandial blood glucose levels were also decreased by
16.3% and 12.5% in 1 g-treated group and by 21.8% and 18.9%
in 2 g-treated group whereas no significant changes were detected
in the control group. It was also found that mean carbohydrate
and protein intake was significantly decreased in both treatment
groups. Taken together, the data are consistent with the notion
that Spirulina is a promising agent as a functional food supplement
for controlling hyperglycerolemia and hypercholesterolemia and
thus reducing cardiovascular risk in the management of type 2
diabetes.
The hypolipidemic benefit of Spirulina was also reported in pa-
tients with nephrotic syndrome and hyperlipidemia [29]. One
group of patients received medication alone whereas the other
group received medication and Spirulina capsules. Supplementa-
tion of Spirulina at a dose of 1 g daily for 2 months resulted in a
reduction in total serum cholesterol, LDL fraction and triglycerides
by 46, 33, and 45 mg/dL, respectively. The ratios of LDL/HDL
and total cholesterol/HDL were also decreased significantly. It was
thus concluded that Spirulina supplementation was an effective
approach to reduce the increased levels of lipids in patients with
hyperlipidemic nephrotic syndrome.
Total and LDL cholesterol levels increase with aging [30,31] as
does the incidence of cardiovascular disease [32]. Three human
clinical studies have been carried out to investigate the therapeu-
tic effects of Spirulina in elderly population [33–35]. In one study
with 12 subjects (6 male and 6 female) between the ages 60 and
75 [33], subjects received a supplement of Spirulina at a dose of
7.5 g/day for 24 weeks. Plasma concentrations of triglycerides,
total cholesterol and LDL fraction were decreased after 4 weeks
of the supplementation while no changes were observed in di-
etary intake and anthropometric parameters. It was also noticed
that no differences in the hypolipidemic effects of Spirulina were
observed between mild hypercholesterolemic (cholesterol at or
above 200 mg/dL) and normocholesterolemic subjects (cholesterol
below 200 mg/dL). The second before-and-after trial included 26
elderly women aged over 60 with hypercholesterolaemic condi-
tion (serum total cholesterol above 200 mg/dL) [34]. Intake of
Spirulina at a dose of 7.5 mg/day for 8 weeks resulted in a sig-
nificant reduction in serum levels of total cholesterol, LDL choles-
terol and oxidized LDL. In addition, apolipoprotein B levels were
also decreased. The most recent clinical trial was a randomized,
double-blinded, and placebo-controlled study [35]. Seventy-eight
subjects between the ages 60 and 87 were randomly assigned into
a study or placebo group. After consumption of Spirulina at a dose
of 8 g/day for 16 weeks, total plasma cholesterol and LDL fraction
Cardiovascular Therapeutics 28 (2010) e33–e45 
c 2010 Blackwell Publishing Ltd
17555922, 2010, 4, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/j.1755-5922.2010.00200.x by Ministry Of Health, Wiley Online Library on [31/10/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
Hypolipidemic, Antioxidant, and Antiinflammatory Activities of Microalgae Spirulina
were significantly reduced in female subjects whereas the lower-
ing effect on plasma total cholesterol and LDL fraction was not
statistically significant in male subjects. The levels of HDL fraction
and triglycerides did not change after the intervention in both men
and women. The data from those clinical trials largely support the
notion that Spirulina supplement is beneficial for managing aging-
induced alterations in lipid profile in the elderly population.
Taken together, although differences in study design, sample
size and patient conditions resulting in minor inconsistency in re-
sponse to Spirulina supplementation, the cumulative data from
those studies clearly demonstrate the hypolipidemic activity of
Spirulina in human. However, the majority of those human clin-
ical trials are suffered with limited sample size and poor experi-
mental design. Additional clinical trials with large sample size and
high quality experimental design are warranted to confirm the hy-
polipidemic and hypoglycerolemic benefits of Spirulina in various
target populations.
Antioxidant and Antiinflammatory Effects
Oxidative stress and inflammation both contribute to the patho-
genesis of cardiovascular diseases, including atherosclerosis, car-
diac hypertrophy, heart failure and hypertension. Overproduction
of reactive oxygen species (ROS) indicating the oxidative stress
have been observed in those cardiovascular disease conditions
[36]. ROS also contributes to vascular dysfunction and remodeling
through oxidative damages in endothelial cells [37]. In addition,
evidence indicates that LDL oxidation is essential for atherogenesis
[38,39]. On the other hand, the microenvironment present within
the atherosclerotic lesion is proinflammatory. In addition to being
a disorder of lipid metabolism, atherosclerosis is now recognized
as a chronic inflammatory disease [40,41]. Accumulating evidence
demonstrates that excessive inflammation within the arterial wall
is a risk factor for cardiovascular diseases and can promote athero-
genesis. Agents with antioxidant and/or antiinflammatory activity
may prove to be beneficial in combating cardiovascular diseases.
Preclinical Studies
In Vitro Studies
A number of studies have reported the antioxidant and/or an-
tiinflammatory activities of Spirulina or its extracts in vitro and
in vivo, suggesting that Spirulina may provide a beneficial effect
in managing cardiovascular conditions. In a study with neuroblas-
toma SH-SY5Y cells [42], the effects of Spirulina protean extract
on iron-induced oxidative stress were investigated. Spirulina treat-
ment protected the activity of the cellular antioxidant enzymes
including glutathione peroxidase (GPX), selenium-dependent glu-
tathione peroxidase (GPX-Se), and oxidized glutathione reductase
(GR), and increased glutathione levels reduced in response to iron
insult. The results clearly demonstrated the antioxidant activity of
Spirulina extract. In a recent in vitro study [43], the antioxidant
and antiinflammatory properties of four different Spirulina prepa-
rations were evaluated with a cell-free as well as a cell-based as-
say. It was found that Spirulina dose-dependently inactivated free
e37

Hypolipidemic, Antioxidant, and Antiinflammatory Activities of Microalgae Spirulina
superoxide radicals generated during an oxidative burst. Equally
significant, Spirulina dose-dependently reduced the metabolic ac-
tivity of functional neutrophils, indicating the antiinflammatory
activity.
Tissue homogenates were used in several in vitro studies to as-
sess the antioxidant activity of Spirulina. In an early study [44],
the antioxidant effect of methanolic extract of Spirulina on spon-
taneous lipid peroxidation of rat brain homogenate was investi-
gated. It was showed that Spirulina extract dramatically inhibited
the production of thiobarbituric acid reactive substances (TBARS),
such as malondialdehyde (MDA), by almost 95%, indicating the
potent antioxidant activity of Spirulina. Fluorouracil (5-FU) is an
anticancer drug with cardiac toxicity and such cardiotoxicity is
resulted from 5-FU-induced impairment in the myocardial an-
tioxidant defense system, leading to cardiac peroxidation [45]. To
evaluate the protective effects of Spirulina on 5-FU-induced lipid
peroxidation, liver homogenate from goat was exposed to 5-FU or
5-FU and Spirulina water extract [46]. As expected, 5-FU caused
an increase in biomarkers of lipid peroxidation, MDA and 4-
hydroxy-2-nonenal (4-HNE), and a decrease in glutathione and
nitric oxide content. However, Spirulina water extract significantly
reduced the levels of MDA and 4-HNE, and increased the reduced
content of glutathione. It was thus concluded that water extract of
Spirulina significantly suppressed 5-FU-induced lipid peroxidation.
Cardiovascular diseases, such as hypertention, atherosclosis,
and ischemic injury, are associated with altered endothelium func-
tion [47]. Vascular tone modification is an important function
of the endothelium achieved by the synthesis and release of ei-
ther vasodilating or vasoconstricting agents. Studies have demon-
strated a dysfunction in nitric oxide synthesis and release, and an
increased secretion of endothelium derived contracting factors in
those disease conditions [48,49]. On the other hand, both LDL
and oxidized-LDL are inhibitors of the endothelium dependent
vasodilator responses [50]. Two studies with rat aorta rings were
carried out to evaluate the effects of Spirulina on vascular tone.
In one study [51], ethanol extract of Spirulina dose-dependently
decreased the contractile response of the aortic ring to vasocon-
stricting agent phenylephrine (PE) whereas enhanced the relax-
ation response to vasodilating agent carbachol, consistent with the
notion that Spirulina extract increased the basal synthesis and/or
release of nitric oxide by the endothelium and cyclooxygenase-
dependent vasoconstricting prostanoid by vascular smooth muscle
cells. Similar findings were obtained in a recent study with aortic
rings from fructose-induced obese rats [52]. Ethanolic extract of
Spirulina significantly decreased PE-induced vasocontriction in a
dose-dependent manner whereas no effects on carbachol-induced
vasodilation were observed. The results suggested that ethanolic
Spirulina extract increased the synthesis and release of nitric ox-
ide but inhibited the synthesis and release of a cyclooxygenase-
dependent vasoconstrictor metabolite of arachidonic acid.
In Vivo Studies
A number of animal studies have been carried out to evaluate
the antioxidant and/or antiinflammatory activities of Spirulina.
In one study with aged male rats [53], Spirulina reversed age-
related increase in proinflammatory cytokines in cerebellum, such
e38
17555922, 2010, 4, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/j.1755-5922.2010.00200.x by Ministry Of Health, Wiley Online Library on [31/10/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
R. Deng and T.-J. Chow
as tumor necrosis factor-alpha (TNFα) and TNFβ. Spirulina supple-
mentation also significantly decreased the oxidative marker MDA
whereas increased the cerebellar beta-adrenergic receptor func-
tion which was reduced by aging. The data thus demonstrated the
antioxidant and antiinflammatory activities of Spirulina in aged
rats.
Doxorubicin (DOX) is an anthracyclin antibiotic primarily used
in the treatment of cancers. However, its application is limited
due to its cardiac toxicity. The generation of ROS, lipid peroxida-
tion, iron-dependent oxidative damage leading to mitochondrial
dysfunction have been implicated in DOX-induced cardiotoxicity
[54,55]. To determine whether Spirulina has cardioprotective ac-
tivity in DOX-induced cardiotoxicity, mice were treated with DOX
alone or DOX with Spirulina [56]. As expected, mice administrated
with DOX exhibited severe cardiac pathologies. However, feeding
of Spirulina at a dose of 250 mg/kg significantly decreased the mor-
tality, ascites and lipid peroxidation; normalized the antioxidant
enzymes levels; and minimized the microscopic damages to the
heart. The data indicated that Spirulina had a protective effect on
cardiotoxicity induced by DOX, most likely through its antioxidant
activity.
As described previously, Spirulina extracts increased the basal
synthesis and release of nitric oxide and cyclooxygenase-
dependent vasoconstricting agent prostanoid by the endothelium
in vitro [51,52]. Such findings were confirmed in two animal stud-
ies in vivo. In one early study with rats [57], feeding of a con-
trolled diet containing 5% Spirulina significantly decreased the
maximal tension of the aorta rings developed in response to vaso-
constrictor PE. On the other hand, supplementation with Spirulina
significantly increased the maximal relaxation in response to va-
sodilating agent carbachol. The data thus indicated that Spirulina
increased the synthesis and release of endogenous vasodilating
agents, such as nitro oxide, whereas decreased the synthesis and
release of vasoconstricting agents, such as eicosanoid, leading to
decreased vascular tone. Consistent results were obtained from an-
other study with rats [58], in which feeding a diet containing 5%
Spirulina prevented the decrease of the endothelium-dependent
vasodilator responses of the aorta rings induced by a high fructose
intake.
In addition, a large number of animal studies were carried out
to investigating the preventive or protective effects of Spirulina in-
take on environmental toxicant, chemical, heavy metal or drug-
induced oxidative stress and inflammation. Those studies were
summarized in Table 2 [59–73]. Accumulative data from those
studies concluded that Spirulina ingestion significantly relieved
or totally prevented the oxidative stress or inflammation, and
their associated pathological damages induced by insulting com-
pounds. Although those studies were not directly investigating
Spirulina’s effects on cardiovascular conditions, the findings clearly
demonstrated the antioxidant and antiinflammatory activities of
Spirulina.
Clinical Studies
In contrast to numerous preclinical studies, a limited number
of clinical trials have been carried to evaluate the antioxidant
and/or antiinflammatory activities of Spirulina in human. In one
Cardiovascular Therapeutics 28 (2010) e33–e45 
c 2010 Blackwell Publishing Ltd
 17555922, 2010, 4, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/j.1755-5922.2010.00200.x by Ministry Of Health, Wiley Online Library on [31/10/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
R. Deng and T.-J. Chow Hypolipidemic, Antioxidant, and Antiinflammatory Activities of Microalgae Spirulina

Table 2 Antioxidant and antiinflammatory activities of Spirulina in preclinical studies

Animal Inducing agent Dose of Spirulina Duration Effects of Spirulina or its extracts References

Rats Haloperi-dol 0.18 g/kg Daily 7 weeks Enzymatic and nonenzymatic antioxidants were [59]
significantly improved, and the tardive dyskinesia
induced by haloperidol was decreased
Rats Cisplatin 0.5–1.5 g/kg Daily 5 days Significantly and dose-dependently restored [60]
renal functions damaged by cisplatin. A decrease
in lipid peroxidation with an increase in
glutathione levels, superoxide dismutase, and
catalase activities
Mice Zymosan 0.1 or 0.4 g/kg Daily 8 days The β-glucuronidase that had been increased by [61]
zymosan was significantly reduced.
Histopathological and ultrastructural evaluation
showed inhibition of the inflammatory reaction
with no destruction of cartilage, well-preserved
chondrocytes, normal rough endoplasmic
reticulum and mitochondria
Mice Cyclopho-sphamide 0.25, 0.5, or 1.0 g/kg Daily 5 days All the three doses resulted in a significant [62]
and mitomycin-C reduction in chromosomal damage and lipid
peroxidation with concomitant changes in
antioxidants and detoxification systems.
Rats Lead 1.5 g/kg Daily 30 days A significant decrease in the levels of [63]
malondialdehyde, conjugated diene and
hydroperoxide.
Rats Collagen 0.4 g/kg Daily Up to 45 days Normalized the joint histopathology of [64]
collagen-induced arthritis and decreased lipid
peroxidation. Serum albumin was significantly
elevated accompanied with a decrease in the
serum cholesterol, alkaline phosphatase and acid
phosphatase activities
Rats Cadmium 0.5 g/kg Daily 1 month A marked decrease in lipid peroxidation [65]
accompanied with an increase in endogenous
antioxidants levels. In addition, the
cadmium-induced histopathological changes
were minimized
Rats Gentami-cin 1 g/kg Daily 7 days Significant nephroprotection was achieved by [66]
sulphate decreasing lipid peroxidation and elevating the
levels of glutathione, superoxide dismutase, GPX,
NO. Histological examination confirmed the
nephroprotective effects of Spirulina
Rats CCl4 5% of the diet 2 days A significant reduction in carbon [67]
tetrachloride-induced elevation of serum
aspartate aminotransferase and liver
triacylglycerols values. In addition, a significant
decrease in free fatty acids and thiobarbituric
acid reactive substances was observed
Mice Mercuric chloride 0.8 g/kg Daily 40 days decreased LPO level, serum glutamate [68]
oxaloacetate and serum glutamate pyruvate
transaminase activity along with increase in liver
GSH level. The activities of antioxidants enzymes
superoxide dismutase, catalase, and
glutathione-S-transferase were also
concomitantly restored to near normal level by
Spirulina supplementation to mercuric chloride
intoxicated mice.

Cardiovascular Therapeutics 28 (2010) e33–e45 

c 2010 Blackwell Publishing Ltd e39
 17555922, 2010, 4, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/j.1755-5922.2010.00200.x by Ministry Of Health, Wiley Online Library on [31/10/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
Hypolipidemic, Antioxidant, and Antiinflammatory Activities of Microalgae Spirulina R. Deng and T.-J. Chow

Table 2 Continued

Animal Inducing agent Dose of Spirulina Duration Effects of Spirulina or its extracts References

Mice Complete freund’s 0.8 g/kg Daily 8 days Adjuvant induced arthritis in the paw [69]
adjuvant characterized by a significant increase in tissue
marker lysosomal enzymes, glycoproteins and
the paw volume. All those arthritic alterations
were almost completely normalized by Spirulina
ingestion
Mice Cisplatin and 0.25, 0.5, or 1 g kg Daily 5 days Genotoxicity induced by cisplatin and urethane [70]
urethane was protected by Spirulina, accompanied with a
significant reduction in the extent of lipid
peroxidation and a concomitant increase in the
liver enzymatic (GPx, GST, SOD, CAT) and
nonenzymatic (reduced glutathione) antioxidants
Rats Compound 48/80 or 0.01–1.0 g/kg Daily Single dose Spirulina dose-dependently inhibited compound [71]
antidinitroph-enyl 48/80 or anti-DNP IgE induced allergic reactions.
(DNP) IgE Serum histamine levels and histamine release
from peritoneal mast cells (RPMC) were
dose-dependently decreased by Spirulina. In
addition, the level of cyclic AMP in RPMC was
significantly increased by 70-fold and the
anti-DNP IgE-induced tumor necrosis factor-α
production was inhibited
Rats Cyclospo-rine 0.5 g/kg Daily 17 days Spirulina protected cyclosporine induced- [72]
nephrotoxicity, evidenced by a decrease in
plasma urea and creatinine. A significant
decrease in plasma and local tissue MDA was
observed. In addition, histopathological analysis
revealed that the severe isometric vacuolization
and widening of the interstitium induced by
cyclosporine were completely prevented by
Spirulina.
Mice 1-methyl-4-phenyl- 0.025, 0.05, 0.1, 0.15, 22 days At a dose of 0.15 g/kg, Spirulina partially reversed [73]
1,2,3,6-tetrahydr- or 0.2 g/kg Daily the dopamine-depleting effect of MPTP and
opyridine completely blocked the oxidative stress induced
(MPTP) by MPTP

study with 26 elderly women, intake of Spirulina 7.5 mg/day for
8 weeks significantly decreased serum IL-6 levels and IL-6 pro-
duction from peripheral blood lymphocytes [34], demonstrating
the antiinflammatory activity of Spirulina. In a recent randomized,
double-blind and placebo-controlled study with 78 healthy elderly
subjects [35], supplementation of Spirulina at a dose of 8 g/day for
16 weeks resulted in a significant rise in plasma interleukin (IL)-2
concentrations in both male and female subjects with a concurrent
reduction in IL-6 concentration in male subjects, and an increase
in superoxide dismutase activity in female subjects. Finally, a re-
cent clinical trial with 37 type 2 diabetes patients revealed that
Spirulina ingestion at a dose of 8 g daily for 12 weeks significantly
reduced serum interleukin 6 (IL-6) and oxidative marker MAD
levels [27]. The data from those studies demonstrated the antiox-
idant and antiinflammatory activities of Spirulina in vivo.
It is well established that exercise promotes the production of
reactive oxygen and nitrogen species, which contribute to skele-
tal muscle fatigue and damage [74]. Two clinical trials were con-
ducted to investigate the effects of Spirulina on preventing excise-
induced skeletal muscle fatigue and damage through its antioxi-
dant property. In one study with 16 student volunteers, intake of
a diet containing 5% Spirulina for 3 weeks resulted in a significant
reduction of plasma oxidative marker MDA with a concurrent in-
crease in the blood superoxide dismutase activity [75]. In a recent
study with nine male subjects [76], supplementation of Spirulina
with a daily dose of 8 g for 4 weeks significantly prolonged the
time to fatigue, reduced TBARS induced by excise, and increased
the plasma glutathione, protein carbonyls, catalase, and total an-
tioxidant capacity levels. In addition, ingestion of Spirulina also
significantly decreased carbohydrate oxidation rate by 10.3% and
increased fat oxidation rate by 10.9%. Taken together, the data
indicated that supplementation of Spirulina had preventive effects
on skeletal muscle fatigue and damage mainly through its antiox-
idant activity.
Allergic rhinitis is characterized by allergic airway inflammation
and hyperresponsiveness to nonspecific stimuli, often involving

e40 Cardiovascular Therapeutics 28 (2010) e33–e45 

c 2010 Blackwell Publishing Ltd

R. Deng and T.-J. Chow
activation of mast cells by IgE. To investigate whether Spirulina has
therapeutic effects on alleviating allergic rhinitis through its anti-
inflammatory and antioxidant activities, two human clinical stud-
ies were carried out with allergic rhinitis patients. In a randomized,
double-blinded crossover study [77], intake of Spirulina at a dose
of 2 g/day for 12 weeks reduced IL-4 levels by 32% released from
phytohemagglutinin (PHA)-stimulated peripheral blood mononu-
clear cells whereas no significant changes were observed for inter-
feron gamma (IFNγ ) and IL-2. In another recent trial [78], Spir-
ulina consumption significantly improved the allergic symptoms
compared with placebo, including nasal discharge, sneezing, nasal
congestion and itching. Thus it was concluded that Spirulina was
clinically effective on managing allergic rhinitis through its antiin-
flammatory and/or antioxidant properties.
Mechanism of Action
Hypolipidemic Activity
Although the hypolipidemic effect of Spirulina has been demon-
strated in preclinical and clinical studies, our understanding on its
mechanism of action is almost totally lacking. The active ingredi-
ents in Spirulina responsible for the hypolipidemic activity remain
to be identified. In a study with S. platensis concentrate (SPC), it
was found that SPC could bind cholesterol metabolites bile acids
and decreased cholesterol solubility. Feeding rats with SPC signifi-
cantly increased fecal excretion of cholesterol and bile acid. It was
thus proposed that decreases in intestinal cholesterol and bile acid
absorption following SPC feeding may represent a mechanism for
the hypocholesterolemic action of SPC [79].
Phycocyanin is a water soluble protein and enriched in Spir-
ulina. Ingestion of phycocyanin preparation made from SPC re-
sulted in a significant decrease in serum total cholesterol and
atherogenic index whereas serum HDL cholesterol was concur-
rently increased. It was thus suggested that phycocyanin might
be the active ingredient in Spirulina responsible for the hypolipi-
demic activity [79]. However, addition studies with highly pu-
rified or expressed phycocyanin are required to confirm the
findings.
Antioxidant and Antiinflammatory Effects
Spirulina contains several active ingredients, notably phycocyanin
and β-carotene that have potent antioxidant and antiinflamma-
tory activities. The antioxidant and antiinflammatory properties
of phycocyanin were first reported in 1998 [80,81] and confirmed
by numerous studies thereafter [20,82–92]. Phycocyanin has the
ability to scavenge free radicals, including alkoxyl, hydroxyl, and
peroxyl radicals. It also decreases nitrite production, suppresses
inducible nitric oxide synthase (iNOS) expression, and inhibits
liver microsomal lipid peroxidation [20,80–92]. Using recombi-
nant technology, phycocyanin protein has been expressed and the
antioxidant activity is also demonstrated with the recombinant
phycocyanin protein [93,94].
As antiinflammatory activities, phycocyanin inhibits
proinflammatory cytokine formation, such as TNFα, sup-
presses cyclooxygeanase-2 (COX-2) expression and decreases
Cardiovascular Therapeutics 28 (2010) e33–e45 
c 2010 Blackwell Publishing Ltd
17555922, 2010, 4, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/j.1755-5922.2010.00200.x by Ministry Of Health, Wiley Online Library on [31/10/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
Hypolipidemic, Antioxidant, and Antiinflammatory Activities of Microalgae Spirulina
prostaglandin E(2) production [83,85,88–90]. In addition, phy-
cocyanin has been reported to suppress the activation of nuclear
factor-κB (NF-κB) through preventing degradation of cytosolic
IκB-α [89] and modulate the mitogen-activated protein kinase
(MAPK) activation pathways, including the p38, c-Jun N-terminal
kinase (JNK), and extracellular-signal-regulated kinase (ERK1/2)
pathways [95,96].
Another ingredient of Spirulina, β-carotene, has been reported
to have antioxidant and antiinflammatory activities [97–99]. In
a study to compare β-carotene, vitamin E, and nitric oxide as
membrane antioxidants, it was found that β-carotene protected
against singlet oxygen-mediated lipid peroxidation [97]. Studies
also showed that β-carotene inhibited the production of nitric
oxide and prostaglandin E(2), and suppressed the expression of
iNOS, COX-2, TNF-α, and IL-1β. Such suppression of inflamma-
tory mediators by β-carotene is likely resulted from its inhibition
of NF-κB activation through blocking nuclear translocation of NF-
κB p65 subunit [98]. In addition, β-carotene suppressed the tran-
scription of inflammatory cytokines including IL-1β, IL-6, and IL-
12 in macrophage cell line stimulated by lipopolysaccharide (LPS)
or IFNγ [99].
Safety Profile
Spirulina has been consumed as food by man for long time in
Mexico and Central Africa and is currently used widely as nu-
traceutic food supplement, especially in Asian. Over the history of
Spirulina use by human, it has been generally considered safe to
ingest Spirulina. Consistent with such notion are the results from a
number of animal studies. However, few clinical studies have been
carried out to systemically establish the safety profile of Spirulina in
human.
To determine whether Spirulina feeding have any side effects
on the growth and development of embryo and fetus, four ani-
mal studies with pregnant rats have been conducted [100–103]. In
one study [100], Spirulina was administrated to pregnant rats from
days 1–14, 1–21, and 7–14 of gestation with increasing doses (from
0 to 30 g/100 g body weight). It was found that Spirulina feed-
ing did not change the maternal and fetal weight. No teratogenic-
ity was detected with consumption of Spirulina even with highest
dose and longest duration. Consistent results were obtained with
a similar study in pregnant rats [101]. Supplementation of Spir-
ulina in the diet at the doses much higher than any anticipated
human consumption did not cause any signs of embryotoxic ef-
fects. In another study with rats [102], the effects of Spirulina alone
or in combinations with other supplements on pregnancy were
investigated. Maximal maternal weight gain was associated with
Spirulina/wheat gluten diet whereas wheat gluten diet resulted in
least weight gain. Intake of diet containing Spirulina significantly
increased litter size whereas birth weights of pups were compa-
rable to those from other groups. Finally, a study with pregnant
rats to assess the general reproductive performance showed that
Spirulina feeding did not change body weight of male and female
rats with no signs of toxicity and was not associated with any ad-
verse effects on any measures of reproductive performance includ-
ing fertility, gestation and abnormal pups [103]. Taken together,
it was concluded that Spirulina had no detectable adverse effects
e41

Hypolipidemic, Antioxidant, and Antiinflammatory Activities of Microalgae Spirulina
on reproductive performance, embryo and fetus development and
growth [104].
To evaluate the safety of relatively long-term feeding of Spir-
ulina, mice were fed with a diet containing increasing percentages
(from 0% to 30% w/w) of Spirulina for 13 weeks [105]. Ingestion
of Spirulina had no effects on behavior, food and water intake,
growth, and survival. Hematologic and clinical chemistry analy-
ses revealed no abnormality. In addition, no gross or microscopic
changes were detected with histological evaluation. In a recent
study with short and long-term Spirulina feeding in rodents [106],
feeding mice with high dose of Spirulina (30 g and 10 g/kg body
weight of fresh and dried Spirulina, respectively) for 7 days re-
sulted in no signs of toxicity. In the long-term feeding study, rats
were administrated with Spirulina at various doses for 12 weeks.
Consumption of Spirulina did not cause any changes in behavior,
food and water intake, growth, health status, and measurements
of clinical chemistry [106].
Despite of favorable safety profile in rodents, there were reports
raising the concerns of the safety of Spirulina consumption. A low
level of mercury and other heavy metals were reported in Spirulina
grown in open water source [107]. Consumption of such Spirulina
preparation could lead to increased deposit of mercury and other
heavy metals causing toxic effects. However, with controlled wa-
ter sources for growing Spirulina, commercial Spirulina products
tested contained mercury or lead at the levels much lower than the
guidelines for daily intake of those elements by the WHO’s Food
and Agriculture Organization (FAO) [108]. Certain cyanobacterial
species produce cyanotoxin and contamination of those species in
the Spirulina products may be deleterious for consumers [109].
In a newly reported study, anatoxin-a, a cyanotoxin with acute
neurotoxicity, were detected in 3 of the 39 cyanobacterial samples
[110]. It was thus recommended that quality control of cyanobac-
terial food supplements including Spirulina was required to avoid
potential adverse effects in animals and humans.
Finally, a few rare incidences associated with consumption of
Spirulina supplements in human have been reported. One case of
hepatotoxicity was possibly associated with Spirulina intake [111],
although the patient also took three other medications. A case of
rhabdomyolysis was recently reported as a result of Spirulina in-
take [112]. Finally, an association of Spirulina consumption and
development of a mixed immunoblistering disorder with charac-
teristic features of bullous pemphigoid and pemphigus foliaceus
was reported in an 82-year-old healthy woman [113].
Taken together, Spirulina is generally considered safe for human
consumption supported by its long history of use as food source,
and its favorable safety profile in animal studies. However, rare
cases of side-effects have been reported and should be taken into
consideration. In addition, additional clinical studies are required
to systemically establish the safety profile of Spirulina in human.
Finally, quality control in the growth and process of Spirulina to
avoid contamination is mandatory to guarantee the safety of Spir-
ulina products.
Concluding Remarks
Recently, great attention and extensive studies have been de-
voted to evaluate the therapeutic benefits of Spirulina on var-
e42
17555922, 2010, 4, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/j.1755-5922.2010.00200.x by Ministry Of Health, Wiley Online Library on [31/10/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
R. Deng and T.-J. Chow
ious diseased conditions including hypercholesterolemia, hyper-
glycerolemia, cardiovascular diseases, inflammatory diseases, can-
cer, and viral infections. The cardiovascular benefits of Spirulina
are primarily resulted from its hypolipidemic, antioxidant, and an-
tiinflammatory activities. Data from preclinical studies with var-
ious animal models consistently demonstrate the hypolipidemic
activity of Spirulina. Although differences in study design, sam-
ple size and patient conditions resulting in minor inconsistency
in response to Spirulina supplementation, the findings from hu-
man clinical trials are largely consistent with the hypolipidemic
effects of Spirulina observed in the preclinical studies. However,
most of the human clinical trials are suffered with limited sample
size and some with poor experimental design. Additional clinical
trials with large sample size and high quality experimental design
are warranted to confirm the hypolipidemic benefits of Spirulina
in various target human populations.
The antioxidant and/or antiinflammatory activities of Spirulina
have been demonstrated in a large number of preclinical studies.
However, a limited number of clinical trials have been carried out
so far to confirm such activities in human. Future clinical trials are
required to establish the antioxidant and antiinflammatory bene-
fits in human. In addition, efforts should be taken to standardize
the dose of Spirulina in future human clinical studies. Spirulina is
generally considered safe for human consumption supported by its
long history of use as food source and its favorable safety profile in
animal studies. However, rare cases of side-effects in human have
been reported. Additional clinical studies are required to system-
ically establish the safety profile of Spirulina in human. Quality
control in the growth and process of Spirulina is a key measure-
ment to avoid contamination and guarantee the safety of Spirulina
products. Currently, our understanding on the underlying mech-
anisms for Spirulina’s activities, especially the hypolipidemic ef-
fect, is still limited. Future studies to identify the active ingredients
in Spirulina and uncover the mechanistic insights into Spirulina’s
therapeutic effects will provide the bases for developing new drugs
for preventing or treating hypercholesterolemia and cardiovascu-
lar diseases.
Acknowledgments
The authors’ research is supported in part by the National Insti-
tutes of Health [Grant R01-DK087755] and National Center for
Research Resources [Grant P20-RR016457] (the Rhode Island-
Institutional Development Awards Network of Biomedical Re-
search Excellence grant); and by the Rhode Island Foundation
[Medical Research Grant 20052653].
Conflict of Interest
The authors declare no conflict of interests.
References
1. Sapp J. The prokaryote-eukaryote dichotomy: Meanings and mythology.
Microbiol Mol Biol Rev 2005;69:292–305.
2. Komárek J, Hauer T. CyanoDB.cz—On-line database of cyanobacterial genera.
Worldwide electronic publication, Univ. of South Bohemia and Inst of Botany AS
CR 2009; http://www.cyanodb.cz.
Cardiovascular Therapeutics 28 (2010) e33–e45 
c 2010 Blackwell Publishing Ltd

R. Deng and T.-J. Chow Hypolipidemic, Antioxidant, and Antiinflammatory Activities of Microalgae Spirulina
3. Vonshak A. (editor). Spirulina platensis (Arthrospira): Physiology, cell-biology and
biotechnology. London: Taylor & Francis, 1997.
4. Gershwin ME, Belay A (editors). Spirulina in human nutrition and health. Boca
Raton: CRC Press, 2008.
5. Khan Z, Bhadouria P, Bisen PS. Nutritional and therapeutic potential of
Spirulina. Curr Pharm Biotechnol 2005;6:373–379.
6. Karkos PD, Leong SC, Karkos CD, Sivaji N, Assimakopoulos DA. Spirulina in
clinical practice: Evidence-based human applications. Evid Based Complement
Alternat Med 2008;eCAM:1–4.
7. Ciferri O, Tiboni O. The biochemistry and industrial potential of Spirulina. Ann
Rev Microbiol 1985;39:503–526.
8. Abdulqader G, Barsanti L, Tredici M. Harvest of Arthrospira platensis from
Lake Kossorom (Chad) and its household usage among the Kanembu. J Appl
Phychol 2000;12:493–498.
9. Habib MAB, Parvin M, Huntington TC, Hasan MR. A review on culture,
production, and use of Spirulina as food for humans and feeds for domestic
animals and fish. FAO Fisheries and Aquaculture Circular No.034, 2008.
10. Kulshreshtha A, Zacharia AJ, Jarouliya U, Bhadauriya P, Prasad GB,
Bisen PS. Spirulina in health care management. Curr Pharm Biotechnol
2008;9:400–405.
11. National Cholesterol Education Program (NCEP). Expert panel on detection,
evaluation, and treatment of high blood cholesterol in adults (Adult
Treatment Panel III). Third report of the national cholesterol education
program (NCEP) expert panel on detection, evaluation, and treatment of high
blood cholesterol in adults (Adult Treatment Panel III) final report. Circulation
2002;106:3143–3421.
12. Barter P, Gotto AM, LaRosa JC, et al.; Treating to New Targets Investigators.
HDL cholesterol, very low levels of LDL cholesterol, and cardiovascular
events. N Engl J Med 2007;357:1301–1310.
13. Sharma RK, Singh VN, Reddy HK. Thinking beyond low-density lipoprotein
cholesterol: Strategies to further reduce cardiovascular risk. Vasc Health Risk
Manag 2009;5:793–799.
14. Devi MA, Venkataraman LV. Hypocholesterolemic effect of blue-green algae
Spirulina platensis in albino rats. Ann Nutr Reports Int 1983;28:519–530.
15. Kato T, Takemoto K, Katayama H, Kuwabara Y. Effects of Spirulina (Spirulina
platensis) on dietary hypercholesterolemia in rats. J Jap Soc Nutr Food Sci
1984;37:323–332.
16. Iwata K, Inayama T, Kato T. Effects of Spirulina platensis on plasma lipoprotein
lipase activity in fructose-induced hyperlipidemic rats. J Nutr Sci Vitaminol
(Tokyo) 1990;36:165–171.
17. Torres-Durán PV, Miranda-Zamora R, Paredes-Carbajal MC, Mascher D,
Blé-Castillo J, Dı́az-Zagoya JC, Juárez-Oropeza MA. Studies on the preventive
effect of Spirulina maxima on fatty liver development induced by carbon
tetrachloride, in the rat. J Ethnopharmacol 1999;64:141–147.
18. Blé-Castillo JL, Rodrı́guez-Hernández A, Miranda-Zamora R, Juárez-Oropeza
MA, Dı́az-Zagoya JC. Arthrospira maxima prevents the acute fatty liver
induced by the administration of simvastatin, ethanol and a
hypercholesterolemic diet to mice. Life Sci 2002;70:2665–2673.
19. Rodrı́guez-Hernández A, Blé-Castillo JL, Juárez-Oropeza MA, Dı́az-Zagoya JC.
Spirulina maxima prevents fatty liver formation in CD-1 male and female mice
with experimental diabetes. Life Sci 2001;69:1029–1037.
20. Riss J, Décordé K, Sutra T, et al. Phycobiliprotein C-phycocyanin from
Spirulina platensis is powerfully responsible for reducing oxidative stress and
NADPH oxidase expression induced by an atherogenic diet in hamsters. J Agric
Food Chem 2007;55:7962–7967.
21. Colla LM, Muccillo-Baisch AL, Costa JAV. Spirulina platensis Effects on the
Levels of Total Cholesterol, HDL and Triacylglycerols in Rabbits Fed with a
Hypercholesterolemic Diet. Braz Arch Biol Technol 2008;51:405–411.
22. Nakaya N, Homa Y, Goto Y. Cholesterol lowering effect of Spirulina. Nutr Rep
Int 1988;37:1329–1337.
23. Torres-Duran PV, Ferreira-Hermosillo A, Juarez-Oropeza MA.
Antihyperlipemic and antihypertensive effects of Spirulina maxima in an open
sample of mexican population: A preliminary report. Lipids Health Dis
2007;6:1–8.
24. Ramamoorthy A, Premakumari S. Effect of supplementation of Spirulina on
hypercholesterolemic patients. J Food Sci Technol 1996;33:124–128.
Cardiovascular Therapeutics 28 (2010) e33–e45 
c 2010 Blackwell Publishing Ltd
17555922, 2010, 4, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/j.1755-5922.2010.00200.x by Ministry Of Health, Wiley Online Library on [31/10/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
25. Mani UV, Desai S, Iyer U. Studies on the long-term effect of Spirulina
supplementation on serum lipid profile and glycated proteins in NIDDM
patients. J Nutraceut, Funct Med Foods 2000;2:25–32.
26. Parikh P, Mani U, Iyer U. Role of Spirulina in the Control of Glycemia and
Lipidemia in Type 2 Diabetes Mellitus. J Med Food 2001;4:193–199.
27. Lee EH, Park JE, Choi YJ, Huh KB, Kim WY. A randomized study to establish
the effects of Spirulina in type 2 diabetes mellitus patients. Nutr Res Pract
2008;2:295–300.
28. Kamalpreet K, Rajbir S, Kiran G. Effect of supplementation of Spirulina on
blood glucose and lipid profile of the non-insulin dependent diabetic male
subjects. J Dairying, Foods Home Sci 2008;27:3–4.
29. Samuels R, Mani UV, Iyer UM, Nayak US. Hypocholesterolemic effect of
Spirulina in patients with hyperlipidemic nephrotic syndrome. J Med Food
2002;5:91–96.
30. Heiss G, Tamir I, Davis CE, Tyroler HA. Lipoprotein-cholesterol distributions
in selected North American populations: The Lipid Research Clinics Program
prevalence study. Circulation 1980;61:302–315.
31. Abbott RD, Garrison RJ, Wilson PW, Epstein FH, Castelli WP, Feinleib M,
LaRue C. Joint distribution of lipoprotein cholesterol classes: The Framingham
Study. Arteriosclerosis 1983;3:260–272.
32. Castelli WP, Wilson PW, Levy D, Anderson K. Cardiovascular risk factors in
the elderly. Am J Cardiol 1989;63:12H–19H.
33. Park JY, Kim WY. The effect of Spirulina on lipid metabolism, antioxidant
capacity and immune function in Korean elderly. Korean J Nutr
2003;36:287–297.
34. Kim MH, Kim WY. The change of lipid metabolism and immune function
caused by antioxidant material in the hypercholesterolemin elderly women in
Korea. Korean J Nutr 2005;38:67–75.
35. Park HJ, Lee YJ, Ryu HK, Kim MH, Chung HW, Kim WY. A randomized
double-blind, placebo-controlled study to establish the effects of Spirulina in
elderly Koreans. Ann Nutr Metab 2008;52:322–328.
36. Dhalla NS, Temsah RM, Netticadan T. Role of oxidative stress in
cardiovascular diseases. J Hypertens 2000;18:655–673.
37. Yung LM, Leung FP, Yao X, Chen ZY, Huang Y. Reactive oxygen species in
vascular wall. Cardiovasc Hematol Disord Drug Targets 2006;6:1–19.
38. Steinberg D. Low density lipoprotein oxidation and its pathobiological
significance. J Biol Chem 1997;272:20963–20966.
39. Chisolm GM, Steinberg D. The oxidative modification hypothesis of
atherogenesis: An overview. Free Radic Biol Med 2000;28:1815–1826.
40. Lusis AJ. Atherosclerosis. Nature 2000;407:233–241.
41. Glass CK, Witztum JL. Atherosclerosis. The road ahead. Cell
2001;104:503–516.
42. Bermejo-Bescós P, Piñero-Estrada E, Villar del Fresno AM. Neuroprotection
by Spirulina platensis protean extract and phycocyanin against iron-induced
toxicity in SH-SY5Y neuroblastoma cells. Toxicol In Vitro 2008;22:1496–1502.
43. Dartsch PC. Antioxidant potential of selected Spirulina platensis preparations.
Phytother Res 2008;22:627–633.
44. Miranda MS, Cintra RG, Barros SB, Mancini Filho J. Antioxidant activity of
the microalga Spirulina maxima. Braz J Med Biol Res 1998;31:1075–1079.
45. Simbre C, Duffy A, Dadlani H, Miller L, Lipshultz E. Cardiotoxicity of cancer
chemotherapy: Implications for children. Pediatr Drugs 2005;7:187–202.
46. Ray S, Roy K, Sengupta C. In vitro evaluation of protective effects of ascorbic
acid and water extract of Spirulina plantesis (blue green algae) on
5-fluorouracil-induced lipid peroxidation. Acta Pol Pharm 2007;64:335–344.
47. Landmesser U, Hornig B, Drexler H. Endothelial function: A critical
determinant in atherosclerosis? Circulation 2004;109(Suppl 1):1127–1133.
48. Luscher TF. Endotheliumderived relaxing and contracting factors: Potential
role in coronary artery disease. Eur Heart J 1989;l:847–857.
49. Miyauchi T, Yanagisawa M, Suzuki N, et al. Venous plasma concentrations of
endothelin in normal and hypertensive subjects. Circulation 1989;80(Suppl
II):2280.
50. Andrews HE, Bruckdorkr KR, Dunn RC, Jacobs M. Low density lipoproteins
inhibit endotheliumdependent relaxation in rabbit aorta. Nature
1987;327:237–239.
51. Paredes-Carbajal MC, Torres-Durán PV, Dı́az-Zagoya JC, Mascher D,
Juárez-Oropeza MA. Effects of the ethanolic extract of Spirulina maxima on
e43

Hypolipidemic, Antioxidant, and Antiinflammatory Activities of Microalgae Spirulina
endothelium dependent vasomotor responses of rat aortic rings. J
Ethnopharmacol 2001;75:37–44.
52. Mascher D, Paredes-Carbajal MC, Torres-Durán PV, Zamora-González J,
Dı́az-Zagoya JC, Juárez-Oropeza MA. Ethanolic extract of Spirulina maxima
alters the vasomotor reactivity of aortic rings from obese rats. Arch Med Res
2006;37:50–57.
53. Gemma C, Mesches MH, Sepesi B, Choo K, Holmes DB, Bickford PC. Diets
enriched in foods with high antioxidant activity reverse age-induced decreases
in cerebellar beta-adrenergic function and increases in proinflammatory
cytokines. J Neurosci 2002;22:6114–6120.
54. Xu MF, Tang PL, Qian ZM, Ashraf M. Effects by doxorubicin on the
myocardium are mediated by oxygen free radicals. Life Sci
2001;68:889–901.
55. Doroshow JH. Doxorubicin-induced cardiac toxicity. N Engl J Med
1991;324:843–845.
56. Khan M, Shobha JC, Mohan IK, et al. Protective effect of Spirulina against
doxorubicin-induced cardiotoxicity. Phytother Res 2005;19:1030–1037.
57. Paredes-Carbajal MC, Torres-Durán PV, Dı́az-Zagoya JC, Mascher D,
Juárez-Oropeza MA. Effects of dietary Spirulina maxima on endothelium
dependent vasomotor responses of rat aortic rings. Life Sci
1997;61:PL211–219.
58. Paredes-Carbajal MC, Torres-Durán PV, Rivas-Arancibia S, Zamora-Gonzalez
J, Mascher D, Juárez-Oropeza MA. Effects of dietary Spirulina maxima on
vasomotor responses of aorta rings from rats fed on a fructose-rich diet. Nutr
Res 1998;18:1769–1782.
59. Thaakur SR, Jyothi B. Effect of Spirulina maxima on the haloperidol induced
tardive dyskinesia and oxidative stress in rats. J Neural Transm
2007;114:1217–1225.
60. Kuhad A, Tirkey N, Pilkhwal S, Chopra K. Renoprotective effect of Spirulina
fusiformis on cisplatin-induced oxidative stress and renal dysfunction in rats.
Ren Fail 2006;28:247–254.
61. Remirez D, González R, Merino N, Rodriguez S, Ancheta O. Inhibitory effects
of Spirulina in zymosan-induced arthritis in mice. Mediators Inflamm
2002;11:75–79.
62. Premkumar K, Pachiappan A, Abraham SK, Santhiya ST, Gopinath PM,
Ramesh A. Effect of Spirulina fusiformis on cyclophosphamide and
mitomycin-C induced genotoxicity and oxidative stress in mice. Fitoterapia
2001;72:906–911.
63. Upasani CD, Khera A, Balaraman R. Effect of lead with vitamin E, C, or
Spirulina on malondialdehyde, conjugated dienes and hydroperoxides in rats.
Indian J Exp Biol 2001;39:70–74.
64. Kumar N, Singh S, Patro N, Patro I. Evaluation of protective efficacy of
Spirulina platensis against collagen-induced arthritis in rats. Inflammopharmacol
2009;17:181–190.
65. Karadeniz A, Cemek M, Simsek N. The effects of Panax ginseng and Spirulina
platensis on hepatotoxicity induced by cadmium in rats. Ecotoxicol Environ Saf
2009;72:231–235.
66. Karadeniz A, Yildirim A, Simsek N, Kalkan Y, Celebi F. Spirulina platensis
protects against gentamicin-induced nephrotoxicity in rats. Phytother Res
2008;22:1506–1510.
67. Torres-Dura’n PV, Paredes-Carbajal AMC, Mascher BD, Zamora-Gonza’lez BJ,
Dı’az-Zagoya CJD, Jua’rez-Oropezaa AMA. Protective Effect of Arthrospira
maxima on Fatty Acid Composition in Fatty Liver. Arch Medl Res
2006;37:479–483.
68. Sharma MK, Sharma A, Kumar A, Kumar M. Spirulina fusiformis provides
protection against mercuric chloride induced oxidative stress in Swiss albino
mice. Food Chem Toxicol 2007;45:2412–2419.
69. Rasool M, Sabina EP, Lavanya B. Anti-inflammatory effect of Spirulina
fusiformis on adjuvant-induced arthritis in mice. Biol Pharm Bull
2006;29:2483–2487.
70. Premkumar K, Abraham SK, Santhiya ST, Ramesh A. Protective effect of
Spirulina fusiformis on chemical-induced genotoxicity in mice. Fitoterapia
2004;75:24–31.
71. Kim HM, Lee EH, Cho HH, Moon YH. Inhibitory effect of mast cell-mediated
immediate-type allergic reactions in rats by Spirulina. Biochem Pharmacol
1998;55:1071–1076.
e44
17555922, 2010, 4, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/j.1755-5922.2010.00200.x by Ministry Of Health, Wiley Online Library on [31/10/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
R. Deng and T.-J. Chow
72. Khan M, Shobha JC, Mohan IK, Rao Naidu MU, Prayag A, Kutala VK.
Spirulina attenuates cyclosporine-induced nephrotoxicity in rats. J Appl Toxicol
2006;26:444–451.
73. Chamorro G, Pérez-Albiter M, Serrano-Garcı́a N, Mares-Sámano JJ, Rojas P.
Spirulina maxima pretreatment partially protects against
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity. Nutr Neurosci
2006;9:207–212.
74. Ferreira LF, Reid MB. Muscle-derived ROS and thiol regulation in muscle
fatigue. J Appl Physiol 2008;104:853–860.
75. Lu HK, Hsieh CC, Hsu JJ, Yang YK, Chou HN. Preventive effects of Spirulina
platensis on skeletal muscle damage under exercise-induced oxidative stress.
Eur J Appl Physiol 2006;98:220–226.
76. Kalafati M, Jamurtas A, Nikolaidis MG, et al. Ergogenic and antioxidant
effects of Spirulina supplementation in humans. Med Sci Sports Exerc
2010;42:142–151.
77. Mao TK, Van de Water J, Gershwin ME. Effects of a Spirulina-based dietary
supplement on cytokine production from allergic rhinitis patients. J Med Food
2005;8:27–30.
78. Cingi C, Conk-Dalay M, Cakli H, Bal C. The effects of Spirulina on allergic
rhinitis. Eur Arch Otorhinolaryngol 2008;265:1219–1223.
79. Nagaoka S, Shimizu K, Kaneko H, et al. A novel protein C-phycocyanin plays
a crucial role in the hypocholesterolemic action of Spirulina platensis
concentrate in rats. J Nutr 2005;135:2425–2430.
80. Romay C, Armesto J, Remirez D, González R, Ledon N, Garcı́a I. Antioxidant
and anti-inflammatory properties of C-phycocyanin from blue-green algae.
Inflamm Res 1998;47:36–41.
81. Romay C, Ledón N, González R. Further studies on anti-inflammatory activity
of phycocyanin in some animal models of inflammation. Inflamm Res
1998;47:334–338.
82. González R, Rodrı́guez S, Romay C, et al. Anti-inflammatory activity of
phycocyanin extract in acetic acid-induced colitis in rats. Pharmacol Res
1999;39:55–59.
83. Romay C, Delgado R, Remirez D, González R, Rojas A. Effects of phycocyanin
extract on tumor necrosis factor-alpha and nitrite levels in serum of mice
treated with endotoxin. Arzneimittelforschung 2001;51:733–736.
84. Remirez D, Ledón N, González R. Role of histamine in the inhibitory effects of
phycocyanin in experimental models of allergic inflammatory response. Mediat
Inflamm 2002;11:81–85.
85. Remirez D, Fernández V, Tapia G, González R, Videla LA. Influence of
C-phycocyanin on hepatocellular parameters related to liver oxidative stress
and Kupffer cell functioning. Inflamm Res 2002;51:351–356.
86. Romay Ch, González R, Ledón N, Remirez D, Rimbau V. C-phycocyanin: A
biliprotein with antioxidant, anti-inflammatory and neuroprotective effects.
Curr Protein Pept Sci 2003;4:207–216.
87. Khan M, Varadharaj S, Shobha JC, Naidu MU, Parinandi NL, Kutala VK,
Kuppusamy P. C-phycocyanin ameliorates doxorubicin-induced oxidative
stress and apoptosis in adult rat cardiomyocytes. J Cardiovasc Pharmacol
2006;47:9–20.
88. Patel A, Mishra S, Ghosh PK. Antioxidant potential of C-phycocyanin isolated
from cyanobacterial species Lyngbya, Phormidium and Spirulina spp. Indian J
Biochem Biophys 2006;43:25–31.
89. Riss J, Décordé K, Sutra T, et al. Phycobiliprotein C-phycocyanin from
Spirulina platensis is powerfully responsible for reducing oxidative stress and
NADPH oxidase expression induced by an atherogenic diet in hamsters. J Agric
Food Chem 2007;55:7962–7967.
90. Cherng SC, Cheng SN, Tarn A, Chou TC. Anti-inflammatory activity of
c-phycocyanin in lipopolysaccharide-stimulated RAW 264.7 macrophages. Life
Sci 2007;81:1431–1435.
91. Shih CM, Cheng SN, Wong CS, Kuo YL, Chou TC. Antiinflammatory and
antihyperalgesic activity of C-phycocyanin. Anesth Analg 2009;108:1303–1310.
92. Manconia M, Pendás J, Ledón N, Moreira T, Sinico C, Saso L, Fadda AM.
Phycocyanin liposomes for topical anti-inflammatory activity: In-vitro in-vivo
studies. J Pharm Pharmacol 2009;61:423–430.
93. Ge B, Qin S, Han L, Lin F, Ren Y. Antioxidant properties of recombinant
allophycocyanin expressed in Escherichia coli. J Photochem Photobiol B
2006;84:175–180.
Cardiovascular Therapeutics 28 (2010) e33–e45 
c 2010 Blackwell Publishing Ltd

R. Deng and T.-J. Chow Hypolipidemic, Antioxidant, and Antiinflammatory Activities of Microalgae Spirulina
94. Guan XY, Zhang WJ, Zhang XW, et al. A potent anti-oxidant property:
Fluorescent recombinant alpha-phycocyanin of Spirulina. J Appl Microbiol
2009;106:1093–1100.
95. Khan M, Varadharaj S, Ganesan LP, et al. C-phycocyanin protects against
ischemia-reperfusion injury of heart through involvement of p38
MAPK and ERK signaling. Am J Physiol Heart Circ Physiol
2006;290:H2136–H2145.
96. Li XL, Xu G, Chen T, et al. Phycocyanin protects INS-1E pancreatic beta cells
against human islet amyloid polypeptide-induced apoptosis through
attenuating oxidative stress and modulating JNK and p38 mitogen-activated
protein kinase pathways. Int J Biochem Cell Biol 2009;41:1526–1535.
97. Schafer FQ, Wang HP, Kelley EE, Cueno KL, Martin SM, Buettner GR.
Comparing beta-carotene, vitamin E and nitric oxide as membrane
antioxidants. Biol Chem 2002;383:671–681.
98. Bai SK, Lee SJ, Na HJ, et al. beta-Carotene inhibits inflammatory gene
expression in lipopolysaccharide-stimulated macrophages by
suppressing redox-based NF-kappaB activation. Exp Mol Med
2005;37:323–334.
99. Katsuura S, Imamura T, Bando N, Yamanishi R. beta-Carotene and
beta-cryptoxanthin but not lutein evoke redox and immune
changes in RAW264 murine macrophages. Mol Nutr Food Res
2009;53:1396–1405.
100. Chamorro G, Salazar M, Salazar S. Teratogenic study of Spirulina in rats. Arch
Latinoam Nutr 1989;39:641–649.
101. Chamorro G, Salazar M. Teratogenic study of Spirulina in mice. Arch Latinoam
Nutr 1990;40:86–94.
102. Kapoor R, Mehta U. Effect of supplementation of blue green alga (Spirulina)
on outcome of pregnancy in rats. Plant Foods Hum Nutr 1993;43:29–35.
Cardiovascular Therapeutics 28 (2010) e33–e45 
c 2010 Blackwell Publishing Ltd
17555922, 2010, 4, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/j.1755-5922.2010.00200.x by Ministry Of Health, Wiley Online Library on [31/10/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
103. Salazar M, Chamorro GA, Salazar S, Steele CE. Effect of Spirulina maxima
consumption on reproduction and peri- and postnatal development in rats.
Food Chem Toxicol 1996;34:353–359.
104. Chamorro G, Salazar M, Favila L, Bourges H. Pharmacology and toxicology of
Spirulina alga. Rev Invest Clin 1996;48:389–399.
105. Salazar M, Martı́nez E, Madrigal E, Ruiz LE, Chamorro GA. Subchronic
toxicity study in mice fed Spirulina maxima. J Ethnopharmacol
1998;62:235–241.
106. Hutadilok-Towatana N, Reanmongkol W, Satitit S, Panichayupakaranant P,
Ritthisunthorn P. A subchronic toxicity study of Spirulina platensis. Food Sci
Technol Res 2008;14:351.
107. Johnson PE, Shubert LE. Accumulation of mercury and other elements by
Spirulina (cyanophyceae). Nutr Rep Int 1986;34:1063–1070.
108. Slotton DG, Goldman CR, Franke A. Commercially grown Spirulina found to
contain low levels of mercury and lead. Nutr Rep Int 1989;40:1165–1172.
109. Chorus I, Bartram J (editors): Toxic cyanobacteria in water. Great Britain: WHO,
E&FN Spon, 1999.
110. Rellán S, Osswald J, Saker M, Gago-Martinez A, Vasconcelos V. First detection
of anatoxin-a in human and animal dietary supplements containing
cyanobacteria. Food Chem Toxicol 2009;47:2189–2195.
111. Iwasa M, Yamamoto M, Tanaka Y, Kaito M, Adachi Y. Spirulina-associated
hepatotoxicity. Am J Gastroenterol 2002;97:3212–3213.
112. Mazokopakis EE, Karefilakis CM, Tsartsalis AN, Milkas AN, Ganotakis ES.
Acute rhabdomyolysis caused by Spirulina (Arthrospira platensis). Phytomedicine
2008;15:525–527.
113. Kraigher O, Wohl Y, Gat A, Brenner S. A mixed immunoblistering disorder
exhibiting features of bullous pemphigoid and pemphigus foliaceus associated
with Spirulina algae intake. Int J Dermatol 2008;47:61–63.
e45